Novel analytical approaches for biomarker detection in neonatology

La principal motivación de esta tesis doctoral es el análisis de biomarcadores basados en moléculas pequeñas de relevancia en el periodo neonatal, específicamente, en situaciones de asfixia perinatal y estrés oxidativo. Se han desarrollado métodos analíticos novedosos y se han adaptado para lidiar con los retos que suponen las muestras en neonatología, empleando enfoques mínimamente invasivos y pequeñas cantidades de muestra. Se han implementado diferentes procesados de muestra para el análisis de orina, sangre y leche humana como la extracción en fase sólida y diferentes tipos de desprotenización. Los métodos analíticos desarrollados están basados en: cromatografía líquida acoplada a espectrometría de masas tándem (LC-MS/MS) para el análisis de biomarcadores relacionados con la síntesis de fosfolípidos, biomarcadores de daño oxidativo a ADN, proteínas y lípidos; cromatografía de gases acoplada a espectrometría de masas (GC-MS) para el análisis de biomarcadores del metabolismo energético; espectroscopía Raman amplificada por superficies (SERS) para el análisis de glutatión. Los diferentes métodos desarrollados se han aplicado con éxito en la evaluación temprana de la asfixia perinatal, el análisis de los compuestos relacionados con el metabolismo energético bajo tratamiento de hipotermia terapéutica, el análisis de nuevos biomarcadores de peroxidación lipídica después de la asfixia perinatal, el análisis del estrés oxidativo en leche materna, y el análisis directo de glutatión en micromuestras de sangre. Por tanto, se ha demostrado la aplicabilidad potencial de las tecnologías analíticas avanzadas en la toma de decisiones clínicas.The main motivation of this PhD thesis is the assessment of small molecule biomarkers with relevance in the neonatal period, and more specifically, in situations of perinatal asphyxia and oxidative stress of the newborn. Novel analytical methods have been developed and tailored to deal with the limitations of sampling in the neonatal population, employing minimally invasive approaches and small sample amounts. Different sample pre-processing steps are implemented within the workflows for the analysis of urine, blood, and human milk including Solid Phase Extraction and different deproteinizations. The employed analytical methods are based on Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) for the analysis of phospholipid synthesis-related biomarkers, DNA & protein oxidative damage compounds, and lipid peroxidation products; Gas chromatography-Mass spectrometry (GC-MS) for the analysis of biomarkers of the energy metabolism; and Surface Enhanced Raman Spectroscopy (SERS) for the analysis of glutathione. The different developed methods have been successfully applied in the early assessment of severity of perinatal asphyxia, the analysis of the energy metabolism-related compounds under therapeutic hypothermia treatment, the analysis of novel lipid peroxidation biomarkers after perinatal asphyxia, the analysis of oxidative stress in human milk, and the direct analysis of glutathione in blood microsamples. Therefore, it has been demonstrated the potential applicability of the advanced analytical technologies into the clinical decision-making

Recubrimientos protectores para incrementar la vida en servicio de materiales que operan en condiciones extremas

Esta Tesis Doctoral se titula “Recubrimientos protectores para incrementar la vida en servicio de materiales que operen en condiciones extremas”. En ella se ha explorado la posibilidad de utilizar recubrimientos duros de nitruros de metales de transición para proteger componentes de acero de turbinas de vapor ultrasupercríticas. Así, se aborda la mejora de la eficiencia energética de las centrales termoeléctricas, desde el punto de vista de la Ciencia de los Materiales y de la Ingeniería Metalúrgica. Mediante el aumento de 30ºC y de hasta 7.5 MPa respecto a las centrales ultrasupercríticas más eficientes actualmente instaladas, que trabajan a 620ºC y 30 MPa, se logran obtener rendimientos superiores al 50%. De esta forma se contribuye a mitigar las emisiones de gases de efecto invernadero, responsables del calentamiento global y del cambio climático, en un 25%..

Two rare species recently described in the genus Comatricha

Dos raras especies de Comatricha de reciente descripción. Se estudian dos especies de Comatricha recientemente descritas como nuevas para la ciencia: C. Meandrispora y C. pellucida . Se aportan datos sobre su variabilidad morfológica, preferencias en su fructificación y se amplía su área de distribución penínsular. Se incluyen microfotografias de sus esporocarpos y al MEB de sus caracteres diferenciales mas importantes.Two rare recently described species of the genus Comatricha. Two species of the genus Comatricha recently described as new for the science are studied: C. Meandrispora and C. pellucida. Dates about its morphologic variability and preference regarding its fructification are given. Moreover, the area of its distribution is enlarged. Microphotographs both of sporocarps and more important differential characters under SEM are included

Bounds on the Zγγ couplings from HERA

The possibility of testing trilinear neutral gauge boson couplings in radiative neutral current scattering at HERA is analyzed using a Monte Carlo program that includes the Standard Model at tree level and the anomalous vertices. Acceptance and isolation cuts are applied as well as optimized cuts to enhance the signal from new physics. The bounds on Z\gamma\gamma couplings that can be achieved are not so stringent as present bounds, even for high luminosities, but probe a different kinematical region almost unsensitive to form factors.This work has been partially supported by the CICYT and the European Commission under contract CHRX-CT-92-0004

Two rare species recently described in the genus Comatricha

Dos raras especies de Comatricha de reciente descripción. Se estudian dos especies de Comatricha recientemente descritas como nuevas para la ciencia: C. Meandrispora y C. pellucida . Se aportan datos sobre su variabilidad morfológica, preferencias en su fructificación y se amplía su área de distribución penínsular. Se incluyen microfotografias de sus esporocarpos y al MEB de sus caracteres diferenciales mas importantes.Two rare recently described species of the genus Comatricha. Two species of the genus Comatricha recently described as new for the science are studied: C. Meandrispora and C. pellucida. Dates about its morphologic variability and preference regarding its fructification are given. Moreover, the area of its distribution is enlarged. Microphotographs both of sporocarps and more important differential characters under SEM are included

Corrosion Behavior of VM12-SHC Steel in Contact with Solar Salt and Ternary Molten Salt in Accelerated Fluid Conditions

Ternary low melting point mixtures with the addition of LiNO3 and Ca(NO3)2 have been presented as direct system candidates for CSP technologies due to having better physical and chemical properties than those of Solar Salt. In this study, thermal, physical and chemical properties are measured as is the corrosive behavior of stainless alloy VM12 (Cr 12%) when in contact with Solar Salt, 60% NaNO3-40% KNO3 (wt.%) and ternary 46% NaNO3-19% Ca(NO3)2-35% LiNO3 (wt.%). Gravimetric weight change measurements were performed on the test specimens, which were tested under accelerated fluid conditions (0.2 m s−1) at 500 °C for 2000 h. This research confirms the potential of this novel formulation as a thermal storage medium and validates the suitability of ferritic VM12-SHC stainless steel as a structural material for CSP technology with Solar Salt. Meanwhile, the results obtained by scanning electron microscopy and X-ray diffraction indicate a reduction in the protective character of the oxide layer formed on this alloy when the medium contains calcium and lithium components.Depto. de Ingeniería Química y de MaterialesFac. de Ciencias QuímicasTRUEMinisterio de Ciencia, Innovaciónpu

High Concentration of Protein Oxidation Biomarker O-Tyr/Phe Predicts Better Outcome in Childhood Bacterial Meningitis

Neuronal damage in bacterial meningitis (BM) partly stems from the host´s inflammatory response and induced oxidative stress (OS). We studied the association of cerebrospinal fluid (CSF) biomarkers indicating oxidative damage to proteins with course of illness and outcome in childhood BM in Angola. Ortho-tyrosine/phenylalanine (o-Tyr/Phe), 3-chlorotyrosine/para-tyrosine (3Cl-Tyr/p-Tyr), and 3-nitrotyrosine/para-tyrosine (3NO2-Tyr/p-Tyr) concentration ratios were measured in 79 BM admission CSF samples, employing liquid chromatography coupled to tandem mass spectrometry. Besides death, disease outcomes were registered on Day 7 of treatment and one month after discharge (control visit). The outcome was graded according to the modified Glasgow Outcome Scale (GOS), which considers neurological and audiological sequelae. Children with a o-Tyr/Phe ratio below the median were more likely to present focal convulsions and secondary fever during recovery and suboptimal outcome (GOS < 5) on Day 7 and at control visit (odds ratio (OR) 2.85; 95% CI 1.14–7.14 and OR 5.23; 95% CI 1.66–16.52, respectively). Their most common sequela was ataxia on Day 7 and at control visit (OR 8.55; 95% CI 2.27–32.22 and OR 5.83; 95% CI 1.12–30.4, respectively). The association of a higher admission CSF o-Tyr/Phe ratio with a better course and outcome for pediatric BM points to a beneficial effect of OS

Influence of Puerperal Health Literacy on Tobacco Use during Pregnancy among Spanish Women: A Transversal Study

Abstract: Background: Despite the fact that tobacco use during pregnancy produces adverse perinatal effects, some women continue to smoke. Health literacy (HL) is essential for health outcomes in adults. However, little is known about HL in pregnant women or postpartum women. The study aimed to analyse the relationship between the degree of HL of women during the early puerperium and tobacco use during pregnancy. Methods: A multicentre, descriptive, cross-sectional study was carried out with women in the early puerperium in a region of eastern Spain, between November 2017 and May 2018. Their HL level was obtained using the Newest Vital Sign (NVS) tool. Multivariate logistic models were adjusted to estimate the magnitude of association with tobacco use in pregnancy. Odds ratios (OR) were estimated with a 95% confidence interval. Results: 193 were included in the total. 29.5% (57) of pregnant women smoked tobacco during pregnancy, with a smoking cessation rate of 70.1% (40) while pregnant. 42.0% (81) of pregnant women had inadequate or limited HL. A low level of HL was strongly associated with tobacco use, adjusted by catchment area and age of first pregnancy (LRT p < 0.001; ROC curve = 0.71, 95% CI: 0.64-0.79). Conclusion: A low HL is associated with tobacco consumption during pregnancy. Whether low HL reflects the wide constellation of already-known socioeconomic, political and commercial determinants of tobacco use, or whether incorporating HL support interventions strengthens tobacco cessation activities in pregnancy, warrants further research. Still, it should be considered as essential to understanding the health disparities related to its consumption

Mass spectrometric detection of biomarkers for early assessment of intraamniotic fluid infection

Peer reviewe

Protein Oxidation Biomarkers and Myeloperoxidase Activation in Cerebrospinal Fluid in Childhood Bacterial Meningitis

The immunological response in bacterial meningitis (BM) causes the formation of reactive oxygen and nitrogen species (ROS, RNS) and activates myeloperoxidase (MPO), an inflammatory enzyme. Thus, structural oxidative and nitrosative damage to proteins and DNA occurs. We aimed to asses these events in the cerebrospinal fluid (CSF) of pediatric BM patients. Phenylalanine (Phe), para-tyrosine (p-Tyr), nucleoside 2′-deoxiguanosine (2dG), and biomarkers of ROS/RNS-induced protein and DNA oxidation: ortho-tyrosine (o-Tyr), 3-chlorotyrosine (3Cl-Tyr), 3-nitrotyrosine (3NO₂-Tyr) and 8-oxo-2′-deoxyguanosine (8OHdG), concentrations were measured by liquid chromatography coupled to tandem mass spectrometry in the initial CSF of 79 children with BM and 10 without BM. All biomarkers, normalized with their corresponding precursors, showed higher median concentrations (p < 0.0001) in BM compared with controls, except 8OHdG/2dG. The ratios o-Tyr/Phe, 3Cl-Tyr/p-Tyr and 3NO₂-Tyr/p-Tyr were 570, 20 and 4.5 times as high, respectively. A significantly higher 3Cl-Tyr/p-Tyr ratio was found in BM caused by Streptococcus pneumoniae, than by Haemophilus influenzae type b, or Neisseria meningitidis (p = 0.002 for both). In conclusion, biomarkers indicating oxidative damage to proteins distinguished BM patients from non-BM, most clearly the o-Tyr/Phe ratio. The high 3Cl-Tyr/p-Tyr ratio in pneumococcal meningitis suggests robust inflammation because 3Cl-Tyr is a marker of MPO activation and, indirectly, of inflammation